Cr(VI) induced hepatocyte apoptosis through the CTH/H2S/Drp1 signaling pathway.

Hexavalent chromium [Cr(VI)] is a highly hazardous heavy metal with multiple toxic effects. Occupational studies indicate that its accumulation in humans can lead to liver damage. However, the exact mechanism underlying Cr(VI)-induced hepatotoxicity remains unknown. In this study, we explored the role of CTH/H2S/Drp1 pathway in Cr(VI)-induced oxidative stress, mitochondrial dysfunction, apoptosis, and liver injury. Our data showed that Cr(VI) triggered apoptosis, accompanied by H2S reduction, reactive oxygen species (ROS) accumulation, and mitochondrial dysfunction in both AML12 cells and mouse livers. Moreover, Cr(VI) reduced cystathionine γ-lyase (CTH) and dynamin related protein 1 (Drp1) S-sulfhydration levels, and elevated Drp1 phosphorylation levels at Serine 616, which promoted Drp1 mitochondrial translocation and Drp1-voltage-dependent anion channel 1 (VDAC1) interactions, ultimately leading to mitochondria-dependent apoptosis. Elevated hydrogen sulfide (H2S) levels eliminated Drp1 phosphorylation at Serine 616 by increasing Drp1 S-sulfhydration, thereby preventing Cr(VI)-induced Drp1-VDAC1 interaction and hepatotoxicity. These findings indicated that Cr(VI) induced mitochondrial apoptosis and hepatotoxicity by inhibiting CTH/H2S/Drp1 pathway and that targeting either CTH/H2S pathway or Drp1 S-sulfhydration could serve as a potential therapy for Cr(VI)-induced liver injury.

Risk factors associated with intraoperative persistent hypotension in pancreaticoduodenectomy.

BACKGROUND: Intraoperative persistent hypotension (IPH) during pancreaticoduodenectomy (PD) is linked to adverse postoperative outcomes, yet its risk factors remain unclear. AIM: To clarify the risk factors associated with IPH during PD, ensuring patient safety in the perioperative period. METHODS: A retrospective analysis of patient records from January 2018 to December 2022 at the First Affiliated Hospital of Nanjing Medical University identified factors associated with IPH in PD. These factors included age, gender, body mass index, American Society of Anesthesiologists classification, comorbidities, medication history, operation duration, fluid balance, blood loss, urine output, and blood gas parameters. IPH was defined as sustained mean arterial pressure < 65 mmHg, requiring prolonged deoxyepinephrine infusion for > 30 min despite additional deoxyepinephrine and fluid treatments. RESULTS: Among 1596 PD patients, 661 (41.42%) experienced IPH. Multivariate logistic regression identified key risk factors: increased age [odds ratio (OR): 1.20 per decade, 95% confidence interval (CI): 1.08-1.33] (P < 0.001), longer surgery duration (OR: 1.15 per additional hour, 95%CI: 1.05-1.26) (P < 0.01), and greater blood loss (OR: 1.18 per 250-mL increment, 95%CI: 1.06-1.32) (P < 0.01). A novel finding was the association of arterial blood Ca2+ < 1.05 mmol/L with IPH (OR: 2.03, 95%CI: 1.65-2.50) (P < 0.001). CONCLUSION: IPH during PD is independently associated with older age, prolonged surgery, increased blood loss, and lower plasma Ca2+.

Histology and transcriptomic analysis reveal the inflammation and affected pathways under 2-methylisoborneol (2-MIB) exposure on grass carp.

2-Methylisoborneol (2-MIB) is a common and widely distributed off-flavor compound in water. However, the toxic mechanisms of 2-MIB on aquatic organisms remain largely unexplored. In this study, grass carp larvae were exposed to different concentrations (0, 5, and 20 µg L-1) of 2-MIB for 96 h. The accumulation of 2-MIB in the dorsal muscle was measured. Histological analysis, ultrastructure observations, and transcriptomic sequencing were conducted on the liver tissues. The results showed that 2-MIB accumulated significantly in the fish muscle, with the accumulation increasing as the exposure concentration increased through gas chromatography-mass spectrometry (GC-MS) detection. Histological and ultrastructure observations indicated that 2-MIB caused concentration-dependent inflammatory infiltration and mitochondrial damage in the liver. Transcriptomic analysis revealed lipid metabolism disorders induced by exposure to 2-MIB in grass carp. Additionally, 5 µg L-1 2-MIB affected the neurodevelopment and cardiovascular system of grass carp larvae through extracellular matrix (ECM)-receptor interaction and focal adhesion pathway. Furthermore, several pathways related to the digestive system were significantly enriched, implying that 2-MIB may impact pancreatic secretion function, protein digestion and absorption processes. These findings provide new insights into the potential toxicological mechanisms of 2-MIB.

CLK2 mediates IκBα-independent early termination of NF-κB activation by inducing cytoplasmic redistribution and degradation.

Activation of the NF-κB pathway is strictly regulated to prevent excessive inflammatory and immune responses. In a well-known negative feedback model, IκBα-dependent NF-κB termination is a delayed response pattern in the later stage of activation, and the mechanisms mediating the rapid termination of active NF-κB remain unclear. Here, we showed IκBα-independent rapid termination of nuclear NF-κB mediated by CLK2, which negatively regulated active NF-κB by phosphorylating the RelA/p65 subunit of NF-κB at Ser180 in the nucleus to limit its transcriptional activation through degradation and nuclear export. Depletion of CLK2 increased the production of inflammatory cytokines, reduced viral replication and increased the survival of the mice. Mechanistically, CLK2 phosphorylated RelA/p65 at Ser180 in the nucleus, leading to ubiquitin‒proteasome-mediated degradation and cytoplasmic redistribution. Importantly, a CLK2 inhibitor promoted cytokine production, reduced viral replication, and accelerated murine psoriasis. This study revealed an IκBα-independent mechanism of early-stage termination of NF-κB in which phosphorylated Ser180 RelA/p65 turned off posttranslational modifications associated with transcriptional activation, ultimately resulting in the degradation and nuclear export of RelA/p65 to inhibit excessive inflammatory activation. Our findings showed that the phosphorylation of RelA/p65 at Ser180 in the nucleus inhibits early-stage NF-κB activation, thereby mediating the negative regulation of NF-κB.

When inflammatory stressors dramatically change, disease phenotypes may transform between autoimmune hematopoietic failure and myeloid neoplasms.

Aplastic anemia (AA) and hypoplastic myelodysplastic syndrome are paradigms of autoimmune hematopoietic failure (AHF). Myelodysplastic syndrome and acute myeloid leukemia are unequivocal myeloid neoplasms (MNs). Currently, AA is also known to be a clonal hematological disease. Genetic aberrations typically observed in MNs are detected in approximately one-third of AA patients. In AA patients harboring MN-related genetic aberrations, a poor response to immunosuppressive therapy (IST) and an increased risk of transformation to MNs occurring either naturally or after IST are predicted. Approximately 10%-15% of patients with severe AA transform the disease phenotype to MNs following IST, and in some patients, leukemic transformation emerges during or shortly after IST. Phenotypic transformations between AHF and MNs can occur reciprocally. A fraction of advanced MN patients experience an aplastic crisis during which leukemic blasts are repressed. The switch that shapes the disease phenotype is a change in the strength of extramedullary inflammation. Both AHF and MNs have an immune-active bone marrow (BM) environment (BME). In AHF patients, an inflamed BME can be evoked by infiltrated immune cells targeting neoplastic molecules, which contributes to the BM-specific autoimmune impairment. Autoimmune responses in AHF may represent an antileukemic mechanism, and inflammatory stressors strengthen antileukemic immunity, at least in a significant proportion of patients who have MN-related genetic aberrations. During active inflammatory episodes, normal and leukemic hematopoieses are suppressed, which leads to the occurrence of aplastic cytopenia and leukemic cell regression. The successful treatment of underlying infections mitigates inflammatory stress-related antileukemic activities and promotes the penetration of leukemic hematopoiesis. The effect of IST is similar to that of treating underlying infections. Investigating inflammatory stress-powered antileukemic immunity is highly important in theoretical studies and clinical practice, especially given the wide application of immune-activating agents and immune checkpoint inhibitors in the treatment of hematological neoplasms.

Determination of cyclic adenosine phosphate and protein content in dormant chlamydospore and nondormant chlamydospore of Arthrobotrys flagrans.

Arthrobotrys flagrans, a nematode-eating fungus, is an effective component of animal parasitic nematode biocontrol agents. In the dried formulation, the majority of spores are in an endogenous dormant state. This study focuses on dormant chlamydospore and nondormant chlamydospore of A. flagrans to investigate the differences in cyclic adenosine monophosphate (cAMP) and protein content between the two types of spores. cAMP and soluble proteins were extracted from the nondormant chlamydospore and dormant chlamydospore of two isolates of A. flagrans. The cAMP Direct Immunoassay Kit and Bradford protein concentration assay kit (Coomassie brilliant blue method) were used to detect the cAMP and protein content in two types of spores. Results showed that the content of cAMP in dormant spores of both isolates was significantly higher than that in nondormant spores (p < 0.05). The protein content of dormant spores in DH055 bacteria was significantly higher than that of nondormant spores (p < 0.05). In addition, the protein content of dormant spores of the SDH035 strain was slightly higher than that of nondormant spores, but the difference was not significant (p > 0.05). The results obtained in this study provide evidence for the biochemical mechanism of chlamydospore dormancy or the germination of the nematophagous fungus A. flagrans.

Optically Tunable Electrical Oscillations in Oxide-Based Memristors for Neuromorphic Computing.

The application of hardware-based neural networks can be enhanced by integrating sensory neurons and synapses that enable direct input from external stimuli. This work reports direct optical control of an oscillatory neuron based on volatile threshold switching in V3O5. The devices exhibit electroforming-free operation with switching parameters that can be tuned by optical illumination. Using temperature-dependent electrical measurements, conductive atomic force microscopy (C-AFM), in situ thermal imaging, and lumped element modelling, it is shown that the changes in switching parameters, including threshold and hold voltages, arise from overall conductivity increase of the oxide film due to the contribution of both photoconductive and bolometric characteristics of V3O5, which eventually affects the oscillation dynamics. Furthermore, V3O5 is identified as a new bolometric material with a temperature coefficient of resistance (TCR) as high as -4.6% K-1 at 423 K. The utility of these devices is illustrated by demonstrating in-sensor reservoir computing with reduced computational effort and an optical encoding layer for spiking neural network (SNN), respectively, using a simulated array of devices.

Unraveling trends in schistosomiasis: deep learning insights into national control programs in China.

OBJECTIVES: To achieve the ambitious goal of eliminating schistosome infections, the Chinese government has implemented diverse control strategies. This study explored the progress of the 2 most recent national schistosomiasis control programs in an endemic area along the Yangtze River in China. METHODS: We obtained village-level parasitological data from cross-sectional surveys combined with environmental data in Anhui Province, China from 1997 to 2015. A convolutional neural network (CNN) based on a hierarchical integro-difference equation (IDE) framework (i.e., CNN-IDE) was used to model spatio-temporal variations in schistosomiasis. Two traditional models were also constructed for comparison with 2 evaluation indicators: the mean-squared prediction error (MSPE) and continuous ranked probability score (CRPS). RESULTS: The CNN-IDE model was the optimal model, with the lowest overall average MSPE of 0.04 and the CRPS of 0.19. From 1997 to 2011, the prevalence exhibited a notable trend: it increased steadily until peaking at 1.6 per 1,000 in 2005, then gradually declined, stabilizing at a lower rate of approximately 0.6 per 1,000 in 2006, and approaching zero by 2011. During this period, noticeable geographic disparities in schistosomiasis prevalence were observed; high-risk areas were initially dispersed, followed by contraction. Predictions for the period 2012 to 2015 demonstrated a consistent and uniform decrease. CONCLUSIONS: The proposed CNN-IDE model captured the intricate and evolving dynamics of schistosomiasis prevalence, offering a promising alternative for future risk modeling of the disease. The comprehensive strategy is expected to help diminish schistosomiasis infection, emphasizing the necessity to continue implementing this strategy.

A Prognostic Model for Survival in Patients with Gastric Signet Ring Cell Carcinoma.

INTRODUCTION: The objective of our study was to develop a nomogram to predict overall survival (OS) and cancer-specific survival (CSS) in patients with gastric signet ring cell carcinoma (GSRCC). METHODS: A total of 3,408 GSRCC patients between 1975 and 2017 were screened from the Surveillance, Epidemiology, and End Results (SEER) database and randomly divided into training and validation cohorts. Univariate and multivariate Cox analyses were conducted to identify independent prognostic factors for the construction of a nomogram. The performance of the model was then assessed by the concordance index (C-index), calibration plot, and area under the receiver operating characteristic curve (AUC). Then, the novel nomogram was further assessed by 64 GSRCC patients from our hospital as the external cohort. RESULTS: We identified age, tumor lymph node metastasis (TNM) staging system, surgery, and chemotherapy as significant independent elements of prognosis. On this basis, a nomogram was constructed, with a C-index of OS in the training and validation cohorts of 0.763 (95% CI: 0.751-0.774) and 0.766 (95% CI: 0.748-0.784) and a C-index of CSS of 0.765 (95% CI: 0.753-0.777) and 0.773 (95% CI: 0.755-0.791), respectively. The AUCs of the nomogram for predicting 2- and 5-year OS were 0.848 and 0.885, respectively, and those for predicting CSS were 0.854 and 0.899, respectively, demonstrating the excellent predictive value of the constructed nomogram compared to the traditional AJCC staging system. Similar results were also observed in both the internal and external validation sets. CONCLUSION: The nomogram provided an accurate tool to predict OS and CSS in patients with GSRCC, which can assist clinicians in making predictions about individual patient survival.

Microstructure characterization of different types of chlamydospores in Arthrobotrys flagrans.

The morphological and structural differences of different types of chlamydospore of Arthrobotrys flagrans, a nematophagous fungus, were studied under light microscope and electron microscope to provide a reference for the biological control of parasitic nematodiasis. In this study, A. flagrans isolate F088 dormant chlamydospore and nondormant chlamydospore were selected as the research objects. The structural differences of these spores were observed by optical microscopy through lactol cotton blue, Trypan blue, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) staining. FunXite -1, 4',6-diamidino-2-phenylindole, and calcofluor white staining were used to observe the metabolic activity, cell wall, and nucleus differences of the two types of spores under fluorescence microscope. Ultrastructure of the two kinds of spores was observed using scanning electron microscope (SEM) and transmission electron microscope (TEM). Since lacto phenol cotton blue, trypan blue staining cannot distinguish dormant spores from dead spores, MTT assay was performed. Fluorescence microscopy observation showed that the cytoplasmic metabolic activity of nondormant spores was stronger than that of dormant spores. The nucleus of dormant spores was bright blue, and their fluorescence was stronger than that of nondormant spores. The cell wall of nondormant spores produced stronger yellow-green fluorescence than that of dormant spores. Ultrastructural observation showed that there were globular protuberances on the surface of the two types of spores but with no significant difference between them. The inner wall of dormant spore possesses a thick zona pellucida with high electron density which was significantly thicker than that of nondormant spores, and their cytoplasm is also changed. In this study, the microstructure characteristics of dormant and nondormant chlamydospores of A. flagrans fungi were preliminarily clarified, suggesting that the state of cell wall and intracellular materials were changed after spores entered to dormancy.

Comprehensive mRNA and microRNA analysis revealed the effect and response strategy of freshwater fish, grass carp (Ctenopharyngodon idella) under geosmin exposure.

Geosmin is an environmental pollutant that causes off-flavor in water and aquatic products. The high occurrence of geosmin contamination in aquatic systems and aquaculture raises public awareness, however, few studies have investigated the response pathways of geosmin stress on freshwater fish. In this research, grass carp were exposed to 50 µg/L geosmin for 96 h, liver tissue was sequenced and validated using real-time qPCR. In total of 528 up-regulated genes and 488 down-regulated genes were observed, includes cytochrome P450 and uridine diphosphate (UDP)-glucuronosyltransferase related genes. KEGG analysis showed that chemical carcinogenesis-DNA adducts, metabolism of xenobiotics by cytochrome P450, drug metabolism-cytochrome P450 pathway was enriched. Common genes from the target genes of microRNAs and differential expression genes are enriched in metabolism of xenobiotics cytochrome P450 pathway. Two miRNAs (dre-miR-146a and miR-212-3p) down regulated their target genes (LOC127510138 and adh5, respectively) which are enriched cytochrome P450 related pathway. The results present that geosmin is genetoxic to grass carp and indicate that cytochrome P450 system and UDP-glucuronosyltransferase play essential roles in biotransformation of geosmin. MicroRNAs regulate the biotransformation of geosmin by targeting specific genes, which contributes to the development of strategies to manage its negative impacts in both natural and artificial environments.

Dual elastography to discriminate adjacent stages of fibrosis and inflammation in chronic hepatitis B: A prospective multicenter study.

BACKGROUND AND AIMS: To evaluate the diagnostic performance of dual elastography (dual-elasto) in continuous differentiation of liver fibrosis and inflammation in a large prospective cohort of patients with chronic HBV. APPROACH AND RESULTS: Adults with positive HBsAg for at least 6 months were recruited from 12 medical centers. Participants underwent dual-elasto evaluations. Biopsy was performed 3 days after dual-elasto examination. Four logistic regression models were trained and strung together into series models. Decision trees based on the series models were performed to achieve continuous differentiation of liver fibrosis and inflammation. The influence of inflammation on the fibrosis stage was also evaluated. A total of 560 patients were included in the training set and 240 in the validation set. Areas under the receiver operating characteristic curve of the series model were 0.82, 0.86, 0.93, and 0.96 to predict ≥F1, ≥F2, ≥F3, and F4 in the validation set, which were significantly higher than those of serum markers and shear wave elastography (all p < 0.05), except for the ≥ F1 levels ( p = 0.09). The AUCs of the series model were 0.93, 0.86, 0.95, and 0.84 to predict inflammation stages ≥G1, ≥G2, ≥G3, and G4, respectively. Decision trees realized 5 continuous classifications of fibrosis and inflammation. Inflammation could enhance the mild fibrosis stage classification while showing limited influences on severe fibrosis or cirrhosis diagnosis. CONCLUSIONS: Dual-elasto demonstrated high performance in the continuous discrimination of fibrosis and inflammation in patients with HBV and could be used to diagnose mild fibrosis without the influence of inflammation.

Effects of β-sitosterol on proliferation and apoptosis of colon cancer cell HCT116 / 中国现代医生

@#Objective To investigate the effects of β-sitosterol on the proliferation and apoptosis of colon cancer cell HCT116,and its regulation of on phosphoinositide 3-kinase/protein kinase B(PI3K/Akt)signaling pathway.Methods Cultivated colon cancer cells HCT116 in vitro and divided them into β-sitosterol High(240μmol/L)、medium(120μmol/L)and low-dose(60μmol/L)groups,set control group(0μmol/L).Applied different concentrations of β-sitosterol treatment of HCT116 cells.And 24h later,the cell proliferation and activity were determined by cell counting kit-8(CCK-8)method,the morphological changes observed under a microscope;Cell apoptosis was observed by Hoechst 33342 nuclear staining;Used cell colony formation assy to detect the colony forming ability of HCT116 cells;and Western blot was used to evaluate the expression of PI3K,p-Akt,Akt,Bcl-2 and Bax in cells.Used AutoDock software for molecular docking of β-sitosterol with Akt and PI3K.Results Compared with the control group,β-sitosterol could inhibit the proliferation of colon cancer HCT116 cells in a concentration dependent manner,inhibit their colony forming ability and promote cell apoptosis and inhibit the expression of p-Akt、PI3K、and Bcl-2 proteins in HCT116 cells and promotes the expression of Bax protein.The binding of β-sitosterol with PI3K and Akt proteins is relatively stable.Conclusion β-sitosterol may regulate the proliferation and apoptosis of HCT116 through inhibiting PI3K/Akt signaling pathway.

Frailty and Health-Related Quality of Life in Elderly Patients Undergoing Esophageal Cancer Surgery: A Longitudinal Study

Purpose@#This study aims to elucidate the longitudinal alterations in frailty and health-related quality of life experienced by elderly patients undergoing surgical treatment for esophageal cancer. Additionally, it seeks to ascertain the impact of preoperative frailty on postoperative health-related quality of life over time. @*Methods@#131 patients were included in the prospective study. Patients' frailty and health-related quality-of-life were assessed utilizing the Tilburg and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 at preoperative, 1 week, 1 month, and 3 months, postoperatively. Statistical analyses were performed using generalized estimating equations, repeated-measures analysis of variance, and linear mixed models (LMMs). @*Results@#Out of 131 patients, 28.2% had frailty before surgery, and the prevalence of frailty consistently higher after surgery compared with baseline (67.9%, 51.9%, and 39.7%). There was no significant change in frailty scores in preoperative frail patients within 3 months following surgery (p = .496, p < .999, p < .999); whereas in preoperative non-frail patients, the frailty scores increased at 1 week (p < .001) and then decreased at 1 month (p = .014), followed by no change at 3 months. In addition, preoperative frail patients had significantly worse global quality-of-life (β = −4.24 (−8.31; −.18), p = .041), physical functioning (β = −9.87 (−14.59; −5.16), p < .001), role functioning (β = −10.04 (−15.76; −4.33), p = .001), and social functioning (β = −8.58 (−15.49; −1.68), p = .015), compared with non-frail patients. @*Conclusions@#A significant proportion of participants exhibited a high prevalence of preoperative frailty. These patients, who were preoperatively frail, exhibited a marked reduction in health-related quality-of-life, a more gradual recovery across various functional domains, and an increased symptom burden during the follow-up period. Therefore, it is crucial to meticulously identify and closely monitor patients with preoperative frailty for any changes in their postoperative physiology, role, and social functioning.

Safety and efficacy of linaclotide combined with polyethylene glycol for bowel preparation / 基础医学与临床

Objective To evaluate safety and efficacy of linaclotide combined with polyethylene glycol(PEG)for bowel preparation.Methods A total of 612 patients from Department of Gastroenterology at the Affiliated Hospital of Qingdao University for colonoscopy examination from January to June 2023 were selected.They were divided into group 1(1 L PEG+2 L PEG),group 2(linaclotide+2 L PEG)and group 3(1 L PEG+linaclotide+1 L PEG)by random number table method,with 204 cases in each group.The Ottawa Bowel Preparation Quality Scale(OBPS),the insertion time of colonoscopy,the time of the first defecation,the frequency of defecations,the occurrence of adverse effects and patients'tolerability were compared among the three groups.Results A total of 601 patients completed bowel preparation and accepted colonoscopy.Group 1 exhibited no statistically significant differences to group 2 with regards to OBPS and insertion time.However,Group 2 demonstrated a shorter duration for the time of the first defecation in comparison to both group 1 and group 3(P＜0.05).Group 1 displayed a higher frequency of defecations as compared to Group 2 and Group 3(P＜0.05).The incidence of adverse reactions was significantly lower in group 2 and group 3 than in group 1(P＜0.05).The overall tolerance score of patients in group 1 was low-er than that in group 2 and group 3(P＜0.05).Conclusions The effect of combining 2 L PEG with 290 μg of lina-clotide for bowel preparation before colonoscopy is similar to that of 3 L PEG.It can reduce the incidence of adverse reactions and patients exhibit good tolerance.For patients who are intolerant to a single high-dose administration of PEG,they need divided-dose regimen of 2 L PEG in combination with linaclotide.

Effects of long-term subculture on biological characteristics of bone marrow mesenchymal stem cells / 中国组织工程研究

BACKGROUND:There is still controversy whether human bone marrow mesenchymal stem cells can maintain their biological characteristics,energy metabolism patterns,and multidirectional differentiation potential after long-term expression in vitro.Further comprehensive and systematic research is needed. OBJECTIVE:To evaluate the effects of long-term expansion in vitro on the biological characteristics of mesenchymal stem cells. METHODS:Human bone marrow mesenchymal stem cells cultured to passage 5,10,and 15 in vitro.MTT assay was used to detect cell proliferation ability.Flow cytometry was used to detect cell cycle.The multi-differentiation potential of mesenchymal stem cells was detected by inducing to adipogenic,osteogenic and chondrogenic differentiation.Cell migration and invasion abilities were detected by scratch test and Transwell assay.The mitochondrial oxidative phosphorylation and glycolysis function were analyzed using energy metabolism analyzer.The cell senescence was detected by senescence-associated β-galactosidase staining.The expression levels of p21,p16,and p53 proteins were detected by western blot assay. RESULTS AND CONCLUSION:Bone marrow mesenchymal stem cells at passages 5,10,and 15 grew adherently;the volume of passage 15 mesenchymal stem cells increased and its proliferation ability decreased;the percentage of S-phase cells decreased(P<0.05).With the increase of culture passages,the migration and invasion abilities decreased gradually(P<0.05).There was no significant difference in the differentiation potential,demonstrated by adipogenic,osteogenic and chondrogenesis induction.The ability of oxidative phosphorylation of mitochondria and glycolysis decreased gradually(P<0.05).The number of senescence-associated β-galactosidase-positive cells increased with the increase of passages(P<0.05),and the expression of senescence protein p21,p16,and p53 increased gradually(P<0.05).The results indicated that the biological characterization of mesenchymal stem cells changed after long-term in vitro expansion.Mesenchymal stem cells cultured over 10 passages may have a reduced activity due to increasing senescence.Therefore,bone marrow mesenchymal stem cells cultured less than 10 passages are suitable for clinical research/therapy.

Efficacy of mFOLFOX7 regimen systemic chemotherapy combined with camrelizumab and apatinib for hepatocellular carcinoma with Vp4 portal vain tumor thrombus / 中华消化外科杂志

Objective:To investigate the efficacy of mFOLFOX7 regimen systemic chemo-therapy combined with camrelizumab and apatinib for hepatocellular carcinoma (HCC) with Vp4 portal vain tumor thrombus (PVTT).Methods:The single-arm, open, exploratory clinical study was conducted. The clinicopathological data of 15 HCC patients with Vp4 PVTT who were admitted to the Sun Yat-sen Memorial Hospital of Sun Yat-sen University from April 2021 to October 2023 were collected. There were 14 males and 1 female, aged 48(range, 33-67)years. All patients underwent treatment with mFOLFOX7 regimen combined with camrelizumab and apatinib. Observa-tion indicators: (1) clinical efficacy; (2) survival of patients. Measurement data with skewed distribution were represented as M(rang), and count data were described as absolute numbers or percentages. Results:(1) Clinical efficacy. All 15 patients underwent treatment with mFOLFOX7 regimen combined with camrelizumab and apatinib. According to the response evaluation criteria in solid tumors version 1.1, the ratio of objective response, ratio of complete response, ratio of partial response, ratio of disease control, median progression free survival time and median total survival time of the 15 patients were 10/15, 1/15, 9/15, 15/15, not reached and not reached. The median progression free survival time and median total survival time were both >9 months. According to the modified response evaluation criteria in solid tumors, the ratio of objective response, ratio of complete response, ratio of partial response, ratio of disease control, median progression free survival time and median total survival time of the 15 patients were 12/15, 6/15, 6/15, 15/15, not reached and not reached. The median progression free survival time and median total survival time were both >9 months. Of the 15 patients, 7 cases were successfully treated with conversion therapy with the surgical conversion rate as 7/15, and all of them achieved R 0 resection. The other 6 cases were failed in conversion therapy, and there were 2 cases still undergoing conversion therapy. Of the 7 patients with successful conver-sion therapy, 5 cases achieved complete pathological remission, 1 case achieved major pathological remission with 90% of tumor tissue necrosis, and 1 case achieved complete remission through imaging examination, but new liver lesions appeared in multiple locations during further observation which were surgically removed. Results of histopathology examination on the patient confirmed multiple liver metastases. The proportion of treatment-associated adverse reactions in 15 patients was 13/15, with 7/15 having ≥grade 3 adverse reactions, including diarrhea (3/15), neutropenia (2/15), thrombo-cytopenia (2/15), and elevated aspartate aminotransferase (2/15). One patient may experience ≥1 adverse reaction. All patients were improved after symptomatic treatment. (2) Survival of patients. All 15 patients were followed up for 13.0(range, 2.0-31.0)months. During the follow-up period, 3 patients died. One case died of upper gastrointestinal bleeding after achieving partial remission, with a survival time of 7.5 months. One case died of multiple liver metastases of tumor, with tumors accounting for over 70% volume of liver and a survival time of 9.5 months. One case with multiple liver tumors and bilateral lung metastasis died due to disease progression after achieving partial remission, with a survival time of 13.5 months. The postoperative follow-up time for 7 patients undergoing surgical treatment was 14.0(range, 2.0-25.0)months. Of the 7 patients, 1 case experien-ced tumor recurrence 20.0 months after surgery, and 6 cases had no recurrence at last time of the follow-up (3 cases completed treatment and entered follow-up observation). The longest survival time was 31.0 months. Conclusion:The mFOLFOX7 regimen systemic chemotherapy combined with camrelizumab and apatinib for HCC with Vp4 PVTT is safe and feasible.

Evaluation and Consideration on Equity in Health Technology Assessment / 中国卫生经济

Health technology assessment(HTA)is an important tool to inform health decision-making.Although highly related to ethical issues in the context of HTA,equity has attracted much attention from the academia,a consensus has not yet been reached on how to define and evaluate equity in China and abroad.It introduces the concept of equity,pointes out the necessity to realize health equity and the reflection of equity in healthcare sector,and further elaborates four ways to consider equity,and described the official practice of equity in HTA at home and abroad.It proposes several suggestions for China's HTA:considering equity in HTA and the discussion of equity should depend on specific decision-making scenarios;clarifying what health measurement perspective should be adopted before measuring health equity;paying attention to the value judgment of equity adopted by various stakeholders;conducting basic researches on the general population's preference for health measurement perspectives and value judgments of equity in China in a gesture to improve the evaluation system of equity in HTA.

Application of DDPM in artificial intelligence image data augmentation of medical device / 中国医学装备

Medical device imaging data augmentation is a method of expanding existing datasets by generating new data samples,which is of great significance for improving the performance of artificial intelligence(AI)medical device-related models and clinical application effects.However,traditional data augmentation methods are usually limited by the quality,realism,and diversity of generated samples.Denoising diffusion probabilistic model(DDPM)is a generative model based on the noise diffusion process,and its main idea is to generate samples with high quality by modelling the sampling process of the target distribution as a process of progressive denoising from the noise distribution.The basic principles and working mechanisms of DDPM were reviewed,the application scenarios of this method in AI medical device data augmentation were analyzed,and its advantages,challenges,and future development directions were explored to provide a reference for the field of AI medical device data augmentation.

Analysis of tissue distribution of metabolites in Crocus sativus L. corms based on DESI mass spectrometry imaging technique / 药学实践与服务

Objective To explore the distribution characteristics of endogenous metabolites in Crocus sativus L. corms from different origins. Methods A method based on desorption electrospray ionization mass spectrometry imaging and optimized sample pretreatment was developed for directly visualize metabolites in C. sativus corms. Results In situ characterization of metabolites such as flavonoids, organic acids, amino acids, carotenoids, and cyclic enol ether terpene glycosides was achieved. L-Citruline, phenylacetylglycine, sativol, and geniposide were specifically distributed in the corms. Apigenin 7-（6''-O-acetyl）-glucoside, isorhamnetin-3-O-β-D-Glucoside, dhurrin 6'-glucoside, and Apigenin 7-O-diglucuronide were mainly distributed in the terminal bud. For compounds distributed in the corms, the highest abundance was found in corms from Shanghai, followed by Zhejiang and the lowest from Anhui. Conclusion The distribution of metabolites in different parts of C. sativus corms from different origins and the same origin varies significantly. Flavonoids and flavonoid derivatives such as isorhamnetin-3-O-β-D-Glucoside and apigenin derivatives are mainly distributed in the terminal buds, in addition, the natural plant protection agent dhurrin 6'-glucoside is also mainly distributed in the terminal corms, whereas amino acids, which are used as energy and material supplies, are mainly accumulated in the corms.